New York gambling house operator Johnny O'Clock is junior partner in a posh casino with Guido Marchettis and Chuck Blayden, a crooked cop. But Blayden is trying to cut into the casino's profits and warns Johnny not to interfere with his intention of becoming Marchettis' full partner. Blayden ends his relationship with coat check girl Harriet Hobson, then disappears. Later, Harriet is found dead in her apartment, apparently from suicide. Police Inspector Koch begins an investigation.He questions Johnny, Harriet's sister Nancy, who is infatuated with Johnny, and Johnny's associate, Charlie. When Blayden's body turns up in a nearby river, and when it is learned that Harriet death wasn't suicide but murder by poison, Johnny and Marchettis become prime suspects in both cases.To make matters worse, Pete Marchettis discovers that his wife Nelle may be having an affair with Johnny. Out of jealousy, he sends hired gunmen to kill Johnny in a drive-by shooting while Johnny is driving Nancy to the airport. Johnny, now certain that Marchettis has betrayed him, goes to the casino to end their business partnership.